Отправить статью по E-mail Specific Activity of Recombinant Modified Human Glucagon-Like Peptide 1
- Авторы: Sannikova E.P.1, Bobkova N.V.2, Tatarnikova O.G.2, Yarotskii S.V.1, Askerova E.V.1, Rykalina N.V.1, Yurin V.L.1, Gracheva T.S.1, Klebanov F.A.1, Zalunin I.A.1, Cheperegin S.E.1, Bulushova N.V.1, Kozlov D.G.1
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Учреждения:
- State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center, Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
- Institute of Cell Biophysics, Russian Academy of Sciences
- Выпуск: Том 55, № 7 (2019)
- Страницы: 722-732
- Раздел: Producers, Biology, Selection, and Gene Engineering
- URL: https://journals.rcsi.science/0003-6838/article/view/153089
- DOI: https://doi.org/10.1134/S0003683819070068
- ID: 153089
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Аннотация
An1 original drug, Glypin, has been developed for the treatment of type-II human diabetes mellitus. Its active pharmaceutical substance is a completely biosynthetic, recombinant, modified, human glucagon-like peptide (rmGlp-1) obtained via culturing of E. coli cells. In addition to the GLP-1 portion, which contains the well-known Ala8Gly substitution, the rmGLP-1 protein has an additional amino acid sequence at the C-terminus that includes the heparin-binding peptide of human HB-EGF. Preclinical testing of Glypin specific activity (with Lixumia as a reference drug) was performed. A commercial preparation of Lixumia served as the main reference drug for comparison with the specific activity of Glypin. During preclinical studies of both medicines, it was shown that Glypin and Lixumia have similar mechanisms, power, and time of action upon subcutaneous and intramuscular introductions, as well as comparable therapeutic effects under long-term use. Based on these data, the subcutaneous injection was selected as the main therapeutic method of Glypin administration; the minimal effective dose for Glypin preclinical study was established as 100 μg/kg body mass, and a single dose for human treatment was defined as 0.75 and 1.5 mg. The intranasal introduction of Glypin was observed to have a statistically reliable positive effect on the cognitive capacities of a mouse with Alzheimer’s disease model. The similarity of the characteristics of Glypin and Lixumia shown in our study make it possible to expect that they will have equal therapeutic efficacy with daily use of a single dose.
Об авторах
E. Sannikova
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Россия, Moscow, 117545
N. Bobkova
Institute of Cell Biophysics, Russian Academy of Sciences
Email: dg_kozlov@genetika.ru
Россия, Pushchino, Moscow oblast, 142290
O. Tatarnikova
Institute of Cell Biophysics, Russian Academy of Sciences
Email: dg_kozlov@genetika.ru
Россия, Pushchino, Moscow oblast, 142290
S. Yarotskii
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Россия, Moscow, 117545
E. Askerova
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Россия, Moscow, 117545
N. Rykalina
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Россия, Moscow, 117545
V. Yurin
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Россия, Moscow, 117545
T. Gracheva
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Россия, Moscow, 117545
F. Klebanov
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Россия, Moscow, 117545
I. Zalunin
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Россия, Moscow, 117545
S. Cheperegin
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Россия, Moscow, 117545
N. Bulushova
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
Россия, Moscow, 117545
D. Kozlov
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Автор, ответственный за переписку.
Email: dg_kozlov@genetika.ru
Россия, Moscow, 117545
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